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Functional analysis of the transcriptional activator encoded by the maize B gene: evidence for a direct functional interaction between two classes of regulatory proteins.

The B, R, C1, and Pl genes regulating the maize anthocyanin pigment biosynthetic pathway encode tissue-specific transcriptional activators. B and R are functionally duplicate genes that encode proteins with the basic-helix-loop-helix (b-HLH) motif found in Myc proteins. C1 and Pl encode functionally duplicate proteins with homology to the DNA-binding domain of Myb proteins. A member of the b-HLH family (B or R) and a member of the myb family (C1 or Pl) are both required for anthocyanin pigmentation. Transient assays in maize and yeast were used to analyze the functional domains of the B protein and its interaction with C1. The results of these studies demonstrate that the b-HLH domain of B and most of its carboxyl terminus can be deleted with only a partial loss of B-protein function. In contrast, relatively small deletions within the B amino-terminal-coding sequence resulted in no trans-activation. Analysis of fusion constructs encoding the DNA-binding domain of yeast GAL4 and portions of B failed to reveal a transcriptional activation domain in the B protein. However, an amino-terminal domain of B was found to recruit a transcriptional activation domain by an interaction with C1. Formation of this complex resulted in the activation of a synthetic promoter containing GAL4 recognition sites, demonstrating that this interaction does not require the normal target promoters for B and C1. B and C1 fusions with yeast GAL4 DNA-binding and transcriptional activation domains were also found to interact when synthesized and assayed in yeast. The domains responsible for this interaction map to a region that contains the Myb homologous repeats of the C1 protein and to the amino terminus of the B protein, which does not contain the b-HLH motif. These studies suggest that the regulation of the maize anthocyanin pigmentation pathway involves a direct interaction between members of two distinct classes of transcriptional activators.

Anthocyanins

Functional analysis of mononuclear cells infiltrating into tumors: establishment of a new system to obtain functionally active tumor-infiltrating cells.

We have demonstrated that tumor-infiltrating T cells play a crucial role in tumor growth. In order to investigate the precise function of tumor-infiltrating cells, we avoided the use of any enzyme for separation of tumor-infiltrating cells from the solid tumor mass and established a new system in which we could easily obtain functionally active tumor-infiltrating cells in large amounts from the peritoneal cavity of T-9 gliosarcoma-sensitized rats. In this system, viable T-9 cells were intraperitoneally administered and peritoneal exudate cells were recovered. Importantly, cells obtained from the intraperitoneal cavity are phenotypically and functionally indistinguishable from those obtained from subcutaneous tumor masses. Furthermore, injection of purified lymphocyte migration factor-b resulted in the accumulation of CD8 (+) cytotoxic T cells in the peritoneal cavity. Therefore, this system also provides a means by which the in vivo function of chemotactic factor can be tested.

Animals

High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.

The efficacy of budesonide (800 micrograms b.d.) and beclomethasone dipropionate (750 micrograms b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV1, FVC, PEF or the histamine PC20. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.

Administration, Inhalation

Executive function deficits in high-functioning autistic individuals: relationship to theory of mind.

A group of high-functioning autistic individuals was compared to a clinical control group matched on VIQ, age, sex and SES. Significant group differences were found on executive function, theory of mind, emotion perception and verbal memory tests, but not on spatial or other control measures. Second-order theory of mind and executive function deficits were widespread among the autistic group, while first-order theory of mind deficits were found in only a subset of the sample. The relationship of executive function and theory of mind deficits to each other, and their primacy to autism, are discussed.

Adolescent

Left ventricular function in diabetes mellitus. II: Relation between clinical features and left ventricular function.

We have shown a close relation between clinical microvascular complications and abnormalities of left ventricular function in 185 established diabetics without clinical heart disease. In 50 insulin-dependent diabetics who presented at under 20 years of age there was a correlation between the duration of diabetes and the isovolumic relaxation time, minimal dimension to mitral valve opening, and ratio of pre-ejection period to left ventricular ejection time. Diabetics with mild microvascular complications were similar to diabetics with no complications except for minor prolongation of the diastolic time intervals. Those with severe complications were significantly different from diabetes with milder complications and normal controls in all variables of left ventricular function. A close relation between left ventricular function and the microvascular complications index (code 0 when no complications to code 7 when all present and severe) was found for the following variables: isovolumic relaxation time, the interval from minimal dimension to mitral valve opening, ratio of pre-ejection period to left ventricular ejection time, and pre-ejection period index. It is concluded that in diabetes abnormalities of left ventricular function are related to duration of disease and complications; and that a diabetic specific heart muscle disorder occurs frequently in patients with severe microvascular complications.

Adult

Effects of L-canavanine on immune function in normal and autoimmune mice: disordered B-cell function by a dietary amino acid in the immunoregulation of autoimmune disease.

This study reports the effects in vitro and in vivo of L-canavanine (LCN), an amino acid found in commonly consumed legumes, on immune function in normal and autoimmune mice. L-Canavanine in high doses effectively blocks all DNA synthesis in vitro within 24 h. At lower doses, LCN affects B-cell function of autoimmune New Zealand Black/New Zealand White (NZB/NZW)F1 mice, inhibiting [3H]thymidine incorporation in response to B-cell mitogens, and pokeweed-induced intracytoplasmic immunoglobulin synthesis. LCN stimulates intracytoplasmic immunoglobulin (IgG greater than IgM). T-cell functions such as lymphoproliferation in response to concanavalin A or phytohemagglutinin and T-cell cytotoxicity are not affected. Suppression of the lipopolysaccharide response by LCN is removed by the addition of fresh B cells. Addition of the amino acid to mouse diet resulted in a decrease in the life-span of the autoimmune NZB and (NZB X NZW)F1 mice and abolished the protective effect of male sex on their survival. The decrease in survival in LCN-treated autoimmune mice correlated with an increase in spontaneous immunoglobulin-secreting cells (IgG greater than IgM) and antinuclear and double-stranded DNA antibodies. The histopathological analyses revealed increased glomerular damage and immunoglobulin deposition in the kidneys of the LCN-treated autoimmune and normal (DBA/2) mice. Ten percent of normal mice developed high titers of autoantibodies after 24 weeks of the diet. These data suggest a dietary amino acid, L-canavanine, affects B-cell function resulting in autoimmune phenomena and providing a new animal model of autoimmunity, a diet-induced systemic lupus erythematosus.

Animals

The effect of high buffer cardioplegia and secondary cardioplegia on cardiac preservation and postischemic functional recovery: a 31P NMR and functional study in Langendorff perfused pig hearts.

High buffer cardioplegia may provide protection against ischemic damage by reducing the extent of intracellular acidosis. Secondary cardioplegia may improve postischemic recovery by restoration of high energy phosphates, ionic gradients, and intracellular pH. To test these hypotheses, pig hearts were arrested with high buffer (150 mM MOPS) cardioplegia or modified St. Thomas' solution II and then kept ischemic at 12 degrees C for 8 h. High energy phosphates and intracellular pH were followed during the period of ischemia, using 31P nuclear magnetic resonance spectroscopy, and functional recovery was followed during reperfusion. The hearts arrested by high buffer cardioplegia showed significantly higher intracellular pH than hearts preserved with St. Thomas' solution, but there were no significant differences in high energy phosphates. There were no significant differences in functional recovery. We found, however, that secondary cardioplegia abolished ventricular fibrillation, and resulted in improved functional recovery after 8 h of ischemic preservation compared with the hearts reperfused with Krebs-Henseleit solution alone. Our results suggest that despite attenuating the decreases in intracellular pH, high buffer cardioplegia does not improve recovery following 8 h of preservation at 12 degrees C. Secondary cardioplegia reduces the incidence of ventricular fibrillation and improves postischemic functional recovery of the myocardium.

Adenosine Triphosphate

Left ventricular function in early primary hypertension. Functional consequences of cardiovascular structural changes.

An increase in left ventricular (LV) wall thickness will lead to decreased LV distensibility during both LV passive filling and left atrial contraction. Reduced LV distensibility will change the filling pattern of the left ventricle, and a proportionally smaller part of the stroke volume will be delivered during the passive filling of the preceding diastole and a larger part during late diastole by a more powerful left atrial contraction. With a more pronounced increase in LV wall thickness a reduced distensibility of venous capacitance vessels (functional or structural) will probably help to preserve LV pump function by influencing LV filling and use of the Frank-Starling mechanism. LV wall stress (peak and end-systolic) is high and LV intrinsic contractility is normal or supernormal in early primary hypertension, as judged from the relationship between end-systolic wall stress and different indices of LV function (fractional shortening, mean velocity of circumferential fiber shortening, ejection fraction). Great differences in peak systolic wall stress may be recorded among groups with comparable values for LV end-systolic wall stress, which may be explained by very different degrees of cardiovascular structural changes, with higher values for peak systolic wall stress seen in hypertension caused by high output than those values seen in hypertension caused by high total peripheral resistance. Signs of supernormal LV systolic function are common in high output hypertension, which is also at least partly due to an increase in LV end-diastolic volume and use of the Frank-Starling mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure

The relationship between cognitive function and liver function in alcoholism.

Thirty alcoholic patients were investigated for evidence of impaired hepatic function and deficits in cognitive functioning, to see if there was any significant relationship between these two complications of alcoholism. Forty-seven per cent had abnormal gamma-glutamyl transpeptidase levels, and 63 per cent had abnormal results on the Category test. Only one significant correlation coefficient was found, between one parameter of hepatic function and one of cognitive function. Possible explanations for this (negative) correlation are discussed, and the value of further study is suggested.

Adult

An assessment of Leydig cell function after bilateral or unilateral efferent duct ligation: further evidence for local control of Leydig cell function.

Leydig cell function was examined in adult male rats at 2 and 4 weeks after bilateral or unilateral efferent duct ligation. Bilateral efferent duct ligation resulted in significantly elevated serum LH levels, an increased size of Leydig cells and an enhanced testosterone response to gonadotropin stimulation in vitro despite a marked loss of LH-hCG receptors. After unilateral ligation of the vasa efferentia, the parameters of Leydig cell function in the ligated testes showed identical changes to those seen after bilateral ligation, whereas such changes were minor or absent in the unligated contralateral testes of the same animals. These results demonstrate that the modifications of Leydig cell function after efferent duct ligation are mainly due to local changes within the testes providing further evidence for an intratesticular control of Leydig cell function.

Animals

Phase-transfer function of the human eye and its influence on point-spread function and wave aberration.

The bidimensional phase-transfer function (PTF) of the human eye has been computed from aerial retinal images of a point test. These images were previously determined by using a recently developed hybrid optical-digital method. Actual PTF data have been obtained directly without linear variations with spatial frequency and have shown great variations among individual subjects. The influence of the PTF on the determination of the point-spread function and the wave-aberration function for emmetropized and slightly astigmatic subjects has been also evaluated. Finally, the effect of pupil size on the PTF was determined by computing these functions from the wave aberration. These results allow us to give a more thorough description of the optical image quality of the human eye and can be used as actual data in subsequent psychophysical studies.

Humans

[Functional asymmetry of the brain and effectiveness of sensorimotor function of oral cavity organs].

It has been established that in healthy persons functional brain asymmetry positively influences the effective performance of sensomotor function of oral cavity organs. Individual brain asymmetry is of considerable importance, the higher it is, the quicker the final results of sensomotor function are achieved. The character of brain asymmetry (right hand or left hand) does not practically influence the performance of sensomotor functions.

Adolescent

Functional and non-functional liver blood flow in patients with liver cirrhosis measured by indocyanine green.

Indocyanine green administration was used in a group of ten patients with liver cirrhosis with portal hypertension to estimate hepatic extraction, liver blood flow and the degree of blood shunting. Extraction coefficients obtained by the hepatic catheterization were well correlated with the pharmacokinetic method. Values of the total liver blood flow measured by the classical method based on Fick's principle were always higher than those evaluated by the pharmacokinetic analysis estimating the functional liver blood flow only. Estimates of the degree of shunting varied between 32.0-78.9% of the total liver blood flow. A statistically significant correlation (r = 0.79) was found between the percentage of the functional fraction of the total liver blood flow and albuminemia. It is suggested that in liver cirrhosis with portal hypertension the reduction of the functional fraction of total liver blood flow is combined with partial impairment of hepatic cell metabolism in the remaining functional areas of the liver. In such a case neither the "intact" nor the "sick hepatocyte" hypotheses are appropriate in their strict sense for the interpretation of the findings.

Humans

[Tests for autonomic functions: sudomotor function].

Sudomotor function tests provide information on the functional state of the sympathetic system innervating skin, the postganglionic fibers of which are cholinergic. Various methods for sweat elicitation and its qualitative or quantitative detection are described here, but most practical combinations vary depending on the purpose of testing and possible pathophysiology of each patient; 1) hyperhidrosis vs. hypo- or anhidrosis, 2) central vs. peripheral or postganglionic lesions, 3) generalized vs. focal disturbances. When these are unknown, thermal sweating of the whole body is most informative. Comparison of thermal and pharmacological sweating enables one to estimate the extent and possible site of sympathetic disturbance. In evaluating the results of sudomotor function tests, factors due to employed methods, age, sex, posture, medication, etc must be taken into consideration. In general, hyperhidrosis is more difficult than hypohidrosis to estimate its underlying mechanism, since the functional relation between the facilitatory hypothalamo-spinal pathway and other central structures still remains largely unknown.

Female

[Abnormalities of respiratory function in civil defence firefighter-submarine divers. Respective role of diving and occupational exposure related to occupational firefighter's functions].

Lung function was studied in 20 firemen-submarine divers (mean age 36 +/- 1.2 years) of the French civil defence undergoing the medical check-up compulsory for professional divers (lung function tests are not systematically performed in ordinary firemen). Compared with the CECA standards: (1) vital capacity (VC) was increased, residual volume (RV) was decreased and total lung capacity (TLC) was unchanged; (2) with the exception of peak respiratory flow, all expiratory flow values (FEV1, MEF50, MEF25) were decreased; (3) the permeability factor (KCO) was decreased. These functional abnormalities were moderately worse in subjects who smoked. Some abnormalities (increased VC, decreased RV) are typical of diving activities, but the deterioration of effort-dependent expiratory flow values and alveolar-capillary diffusion must be ascribed to specific nuisances (fumes, polluants, toxic substances) associated with fireman's activities. Monitoring lung function in all professional firemen therefore seems to be necessary, if not indispensable.

Adult

[Histologic comparison of a functioning and non-functioning filtration membrane with the Molteno implant].

In two patients with a Molteno implant, the filtration membrane was excised 2 and 21 months postoperatively because of uncontrolled elevation of intraocular pressure. This tissue was examined by light and electron microscopy and the findings compared with those of a third functioning Molteno filtration membrane obtained from an enucleation specimen. The most conspicuous differences were the high density and cellularity of the connective tissue of the non-functioning membranes and the frequent cell pyknosis and necrosis in the functioning membrane. In addition, one of the non-functioning membranes showed a condensed cellular layer on the inner surface. There were no inflammatory cell infiltrates in any of the three specimens. We conclude that the variable results of Molteno implants are related to the quantities of tissue components of the filtration membrane.

Adult

[Nutritional assessment of chronic pulmonary emphysema and the significant relation of malnutrition to pulmonary function and respiratory muscle function].

We assessed nutritional status in 30 patients with pulmonary emphysema and 60 healthy controls. The relationship between nutritional status, pulmonary function and respiratory muscle function was also studied. Anthropometric measures, visceral proteins such as PA and RPB, and the Fischer ratio (BCAA/AAA), an index of imbalance of amino acids were significantly lower in the patients. The incidence of moderately malnourished patients with less than 80% of IBW was 40%. The incidence of hyporetinol-binding protein was 40%. 48% of the patients were found to show an amino acid imbalance. These findings suggested that protein-energy malnutrition in association with amino acid imbalance occurred commonly in patients with pulmonary emphysema. FEV1% correlated significantly with some anthropometric indices and the Fischer ratio. Respiratory muscle function, assessed by P1 max, correlated significantly with some anthropometric indices and grasp strength. These results suggested that the degree of airway obstruction and respiratory muscle function was associated with malnutrition characterized by the reduction of the Fischer ratio.

Adult

[Let's study exponential function related to anesthesiology by using computer graphics--Part I: Wash-out exponential function].

A computer simulation is used to analyze physical or biophysical changes related to anesthesiology mostly by computer oriented experts. Recent development in a personal computer and its program, however, has made it possible for more anesthesiologists to have an experience of computer analysis. For example, graphic expression of exponential functions can easily be obtained by using a computer program, such as "Graphnote" by Fukutake Pub. Co. In this literature, the author first explained the wash-out exponential function. Then estimation of changes in the hematocrit and serum protein concentration associated with blood loss during surgery was given as an example of biophysical phenomena related to anesthesiology, to which the wash-out exponential function is applicable for mathematical simulation. Besides, the author demonstrated the way to draw exponential function curves by using "Graphnote", so that the readers can express the curves by themselves.

Anesthesia